Hydrochloric Acid → 1-(3-(Tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

A round bottomed flask was charged with 8-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amine (605a) (4.70 g, 15.06 mmol), tributyl(1-ethoxyvinyl)tin (Sigma-Aldrich) (7.63 mL, 22.58 mmol), Pd2dba3 (Strem Chemicals Inc., 1.38 g, 1.51 mmol), Xphos (Strem Chemicals Inc.) (718 mg, 1.51 mmol), CuI (Strem Chemicals Inc.) (573 mg, 3.01 mmol) and CsF (Sigma-Aldrich) (6.86 g, 45.2 mmol) in dioxane (75 mL). The tube was sealed and heated to 80° C. in an oil bath overnight. LCMS shows enol ether as major product (m/z (ESI, +ve) 304.0 (M+H)+). The reaction mixture was cooled to RT. Concentrated HCl (aq.) (3.14 mL, 37.6 mmol) was added and the mixture stirred at RT for 30 min. The mixture was filtered through Celite and the filter cake was washed with EtOAc and water. The layers were separated and the aq. layer was extracted with EtOAc (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by silica gel chromatography (0-50% EtOAc in hexanes) to provide 1-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (605b) (3.76 g, 13.64 mmol, 91% yield) as a light orange solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (dd, J=9.00, 5.87 Hz, 1H), 7.08 (t, J=9.00 Hz, 1H), 2.70 (s, 3H), 2.49 (s, 3H), 1.52 (s, 9H). 19F NMR (376 MHz, CDCl3) δ ppm −115.38 (s, 1F). m/z (ESI, +ve) 276.1 (M+H)+.

Provenance & Evidence